Surfactants are surface-active agents. This is customarily used to indicate that these are agents that reduce surface tension at an interface between two different materials. In industry, surfactants have long been used as emulsifiers, detergents, lubricants, and wetting agents. Specialized surface-active agents have been developed for these and many other commercial uses.
For more than 40 years we have also known that the body produces surfactants and that these are critical to the optimal performance particularly of the respiratory system. Close to the time of birth, the developing lung is producing more and more pulmonary surfactant in the distal airways (alveoli) and this surfactant prevents these tiny airways from collapsing with each breath. Babies born prematurely often have insufficient production of pulmonary surfactant to keep the lungs open with each breath and this condition is called respiratory distress syndrome of the newborn. Because this disease claims the lives of thousands of prematurely born babies in the United States every year, many investigators have actively identified the components of pulmonary surfactant and developed a variety of surfactant products for administration to the prematurely born infant. This strategy has proven to be highly successful and has drastically reduced mortality in these tiniest of babies. Commercial products developed as pulmonary surfactant for newborns all include the phospholipid chemical, dipalmitoyl phosphatidylcholine (DPPC) as well as spreading agents that either occur naturally (surfactant associated proteins) or that are made artificially. Commercially available pulmonary surfactants are either made by extraction of natural surfactant from newborn animal lungs, generally cows or pigs (Survanta, Curosurf, Infasurf, BLIS), or made entirely in the laboratory from DPPC with other drugs added to enhance spreading, (Exosurf, KL4). All of these agents have been demonstrated to be effective and sale in the treatment of respiratory distress syndrome of the newborn. Pulmonary surfactants have also been administered to a large number of adults with severe respiratory failure due to a condition known as adult respiratory distress syndrome (ARDS). Despite laboratory confirmation that pulmonary surfactant is inactivated in this condition, these clinical trials have generally proven to be disappointing.
The (B. K.) research laboratory* has long focused on understanding the mechanisms of mucus secretion and clearance. In persons with a chronic inflammatory lung diseases including cystic fibrosis, chronic bronchitis, diffuse panbronchiolitis, asthma, and bronchiectasis there is a massive increase in the number and size of mucus secreting glands and cells with markedly increased production of mucus. This problem is made worse by damage to the airways leading to poor clearance of secretions. The build up of these mucus secretions in the airway further increases the amount of infection and inflammation, leads to increased difficulties in breathing, and can be associated with destruction of lung tissue. It is acknowledged that retention of airway secretions is an extremely important factor in the development of chronic lung disease and that medications to enhance clearance of these secretions could be of significant therapeutic benefit with potential to help tens of millions of Americans every year. FNT *The research laboratory of Dr. Bruce K. Rubin, one the inventors
In a series of experiments, we have determined that one of the most important factors influencing the ability to clear mucus secretions from the airways is the adhesiveness of these secretions and that this adhesiveness in turn was largely determined by the surface tension of the secretions in the airway. We then demonstrated that surfactants have the ability to reduce the adhesiveness of secretions and that this in turn, significantly enhances both cough and mucociliary clearance. To put this into perspective, imagine if you will, a child shooting objects from a pea shooter. In order to expel a small wad of sticky substance that attaches to the inside wall of the pea shooter it will take much more effort and airflow from the child then it would to shoot out a pea that has been lubricated by a bit of spit. In this analogy, the pea shooter is the airway, the childis effort represents how hard one must cough to clear secretions, and the substances obviously represent sticky or lubricated airway secretions.
Research has shown that surfactant is not only produced in the alveoli but that surfactant phospholipids are also secreted from the mucus glands and larger airways. We have demonstrated that airway surfactant is essential for mucus clearance and we further demonstrated that in many of the pulmonary diseases associated with hypersecretion there was inactivation of surfactant by inflammatory mediators. Because of this we hypothesized that the administration of pulmonary surfactant to patients with cystic fibrosis or chronic bronchitis would enhance mucus clearance and improve pulmonary function.